Abstract
Biosynthesis of the universal terpenoid precursors, isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), from three acetyl CoA moieties through mevalonate was studied extensively in the 1950s. For several decades, the mevalonate paradigm reigned supreme and a mevalonate origin was attributed to a growing number of natural products, in many cases erroneously. Besides this biosynthetic pathway, the existence of a second one leading to IPP and DMAPP through 1-deoxy-D-xylulose 5-phosphate and 2C-methyl-D-erythritol 4-phosphate was discovered more recently in plants and some eubacteria. This pathway is widely distributed in the bacterial kingdom including major human pathogens, such as Mycobacterium tuberculosis or Helicobacter pylori and is also essential in the malaria vector Plasmodium falciparum. During the last few years, the genes, enzymes, intermediates and mechanisms of the biosynthetic route have been elucidated by a combination of methods including comparative genomics, enzymology, advanced NMR technology and crystallography. The present crystallographic review of enzymes involved in isoprenoid biosynthesis will be useful for understanding the various catalytic mechanisms and could potentially help for structure-based drug design.
Current Protein & Peptide Science
Title: Structure-based Drug Design Targeting Biosynthesis of Isoprenoids: A Crystallographic State of the Art of the Involved Enzymes
Volume: 9 Issue: 2
Author(s): J. de Ruyck and J. Wouters
Affiliation:
Abstract: Biosynthesis of the universal terpenoid precursors, isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), from three acetyl CoA moieties through mevalonate was studied extensively in the 1950s. For several decades, the mevalonate paradigm reigned supreme and a mevalonate origin was attributed to a growing number of natural products, in many cases erroneously. Besides this biosynthetic pathway, the existence of a second one leading to IPP and DMAPP through 1-deoxy-D-xylulose 5-phosphate and 2C-methyl-D-erythritol 4-phosphate was discovered more recently in plants and some eubacteria. This pathway is widely distributed in the bacterial kingdom including major human pathogens, such as Mycobacterium tuberculosis or Helicobacter pylori and is also essential in the malaria vector Plasmodium falciparum. During the last few years, the genes, enzymes, intermediates and mechanisms of the biosynthetic route have been elucidated by a combination of methods including comparative genomics, enzymology, advanced NMR technology and crystallography. The present crystallographic review of enzymes involved in isoprenoid biosynthesis will be useful for understanding the various catalytic mechanisms and could potentially help for structure-based drug design.
Export Options
About this article
Cite this article as:
Ruyck de J. and Wouters J., Structure-based Drug Design Targeting Biosynthesis of Isoprenoids: A Crystallographic State of the Art of the Involved Enzymes, Current Protein & Peptide Science 2008; 9 (2) . https://dx.doi.org/10.2174/138920308783955261
DOI https://dx.doi.org/10.2174/138920308783955261 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
Call for Papers in Thematic Issues
Advancements in Proteomic and Peptidomic Approaches in Cancer Immunotherapy: Unveiling the Immune Microenvironment
The scope of this thematic issue centers on the integration of proteomic and peptidomic technologies into the field of cancer immunotherapy, with a particular emphasis on exploring the tumor immune microenvironment. This issue aims to gather contributions that illustrate the application of these advanced methodologies in unveiling the complex interplay ...read more
Artificial Intelligence for Protein Research
Protein research, essential for understanding biological processes and creating therapeutics, faces challenges due to the intricate nature of protein structures and functions. Traditional methods are limited in exploring the vast protein sequence space efficiently. Artificial intelligence (AI) and machine learning (ML) offer promising solutions by improving predictions and speeding up ...read more
Nutrition and Metabolism in Musculoskeletal Diseases
The musculoskeletal system consists mainly of cartilage, bone, muscles, tendons, connective tissue and ligaments. Balanced metabolism is of vital importance for the homeostasis of the musculoskeletal system. A series of musculoskeletal diseases (for example, sarcopenia, osteoporosis) are resulted from the dysregulated metabolism of the musculoskeletal system. Furthermore, metabolic diseases (such ...read more
Protein Folding, Aggregation and Liquid-Liquid Phase Separation
Protein folding, misfolding and aggregation remain one of the main problems of interdisciplinary science not only because many questions are still open, but also because they are important from the point of view of practical application. Protein aggregation and formation of fibrillar structures, for example, is a hallmark of a ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Recent Progress Towards the Identification of Inhibitors of Mycobacterial Cell Wall Polysaccharide Biosynthesis
Mini-Reviews in Medicinal Chemistry Helminth Infections and Cardiovascular Diseases: Toxocara Species is Contributing to the Disease
Current Cardiology Reviews Preventive Strategies for Ventilator Associated Pneumonia
Current Respiratory Medicine Reviews Comparative Proteome Analysis of <i>Mycobacterium Tuberculosis</i> Strains - H37Ra, H37Rv, CCDC5180, and CAS/NITR204: A Step Forward to Identify Novel Drug Targets
Letters in Drug Design & Discovery Synthesis, Characterization, Antimicrobial, Anti-tubercular, Antioxidant Activities and Docking Simulations of Derivatives of 2-(pyridin-3-yl)-1Hbenzo[ d]imidazole and 1,3,4-Oxadiazole Analogy
Letters in Drug Design & Discovery Protective Mechanisms of Helminths Against Reactive Oxygen Species are Highly Promising Drug Targets
Current Medicinal Chemistry Thalidomide Analogues as Anticancer Drugs
Recent Patents on Anti-Cancer Drug Discovery Comparative Proteome Profiles of Methicillin-Resistant <i>Staphylococcus aureus</i> in Response to Vanillic Acid and 2-Hydroxycinnamic Acid
Current Proteomics Virtual Screening and Synthesis of Novel Antitubercular Agents Through Interaction-Based Pharmacophore and Molecular Docking Studies
Current Computer-Aided Drug Design Response to HAART in Treatment-Naive HIV-Infected Patients with a Prior Diagnosis of Tuberculosis or other Opportunistic Infections
Current HIV Research Programs to Facilitate Tuberculosis Drug Discovery: The Tuberculosis Antimicrobial Acquisition and Coordinating Facility
Infectious Disorders - Drug Targets A Novel Multi-Target Drug Screening Strategy Directed Against Key Proteins of DAPk Family
Combinatorial Chemistry & High Throughput Screening A Review of Molecular Modelling Studies of Dihydrofolate Reductase Inhibitors Against Opportunistic Microorganisms and Comprehensive Evaluation of New Models
Current Pharmaceutical Design Old and New Strategies for the Discovery of Antibacterial Agents
Current Medicinal Chemistry - Anti-Infective Agents The Plant-Type Ferredoxin-NADP+ Reductase/Ferredoxin Redox System as a Possible Drug Target Against Apicomplexan Human Parasites
Current Pharmaceutical Design Identification of Bostrycin Derivatives as Potential Inhibitors of Mycobacterium tuberculosis Protein Tyrosine Phosphatase (MptpB)
Medicinal Chemistry Evaluation of Polyphenolic Profile and Antibacterial Activity of Pomegranate Juice in Combination with Rifampin (R) against MDR-TB Clinical Isolates
Current Pharmaceutical Biotechnology Exploring and Exploiting Gene Networks That Regulate Natural Products Biosynthesis in Actinobacteria
The Natural Products Journal Molecular Interactions in Interleukin and Toll-like Receptor Signaling Pathways
Current Pharmaceutical Design SAR, QSAR and Docking of Anticancer Flavonoids and Variants: A Review
Current Topics in Medicinal Chemistry